PROJECT SUMMARY AND ABSTRACT Alcohol use behaviors and consequences of use fluctuate over time in both clinical and non-clinical populations, but neurobiological mechanisms that can predict these alcohol use behavior changes are not well understood. Alcohol-related behavior changes tend to occur most often during emerging adulthood (ages 18 - 30 years) and can be observed in the full spectrum of drinkers. Even among those with an alcohol use disorder, these changes typically occur outside the context of treatment. The goal of this study is to prospectively examine the role of two promising neurobiological mechanisms of alcohol use behavior change, resting-state functional connectivity (rsFC) of the brain and heart rate variability (HRV), in a sample of non- treatment-seeking emerging adult drinkers. Preliminary findings support the scientific premise for rsFC and HRV as neurobiological mechanisms of alcohol use behavior change. Two aspects of each larger mechanism will be examined. The rsFC analyses will focus on connectivity within the central executive network, a large- scale neural network linked to higher-order executive processing, and connectivity between the amygdala and orbitofrontal cortex, two brain regions linked to emotional processing. The HRV analyses will focus on high- frequency HRV, an index of parasympathetic nervous system activity, and 0.1Hz HRV, an index of communication between the peripheral and central nervous systems. The proposed longitudinal design includes data at three time points: T1, T2, T3. Alcohol behaviors, rsFC, and HRV were assessed at T1 as part of two ongoing studies (2014-2017). The proposed study will re-assess alcohol behaviors via telephone interview at a second time point (T2) and measure alcohol behaviors and HRV in-person at a third time point (T3). Eligible participants (n = 104) were non-treatment-seeking emerging adults at T1. Their alcohol use behaviors at T1 ranged from NIAAA-defined low-risk use to meeting criteria for alcohol use disorder. Aim 1 of the proposed research is to characterize the associations between alcohol behavior, rsFC, and HRV at T1. Aim 2 is to examine the role of T1 rsFC on trajectories of alcohol behaviors across T1, T2, and T3. Aim 3 is to examine the role of T1 HRV on alcohol use behavior change and the bidirectional relationship of HRV and alcohol use over time. Linear regressions will examine cross-sectional relationships at T1 (Aim 1). Hierarchical linear models will test the temporal relationships between rsFC, HRV, and alcohol use (Aims 2 & 3). The knowledge gained from this research can inform new targets of behavioral and pharmacological treatments for alcohol use disorders, which result in over $200 billion of economic burden each year in the United States. Furthermore, results of the proposed research will build a foundation to inform future larger-scale studies on the role of multiple neurobiological mechanisms, and their integration, on alcohol behavior change.